BACKGROUND: Skin tags are dermatological lesions commonly found in the general population and have been associated with diabetes mellitus, obesity, insulin resistance and atherosclerosis. Early detection of patients with insulin resistance may play an important preventive role. OBJECTIVE: To evaluate the association between skin tags in the neck or axillary regions and insulin resistance. METHODS: A cross-sectional study involving adult patients receiving care at a university teaching hospital. Cases were defined as patients with > 5 skin tags in the neck region and/or axillae. Insulin resistance was estimated using the HOMA-IR index. Results were adjusted for the other known covariates of risk for insulin resistance using a multiple logistic regression model. RESULTS: Ninety-eight cases and 103 controls were evaluated. There was no difference between the groups with respect to age or gender. Skin tags were directly associated with HOMA-IR values (odds ratio = 1.4), hypertriglyceridemia and body mass index, irrespective of adjustment for diabetes mellitus, age, skin phototype, gender, family history of diabetes mellitus or hip/waist ratio. Qualitatively elevated HOMA-IR levels (>3.8) were also significantly associated (odds ratio = 7.5). CONCLUSIONS: The presence of multiple skin tags was strongly associated with insulin resistance irrespective of other risk factors.